Triazamacrocyclic NMR contrast agents and methods for their use

Abstract

Compositions for the enhancement of NMR contrast are disclosed which include a complex of a paramagnetic metal selected from the group consisting of gadolinium, manganese, iron, and chromium, with one of a group of triazamacrocyclic ligands. Methods for using such compositions are also disclosed.

I claim: 
     
       1. An NMR contrast agent, comprising a complex of a paramagetic metal selected from the group consisting of gadolinium, manganese, iron, and chromium, with a ligand selected from the group consisting of compounds having the formula ##STR5## where R 1  is selected from the group consisting of: ##STR6## where R 2  is --C q  H 2q+1  ; X is selected from the group consisting of --SO 3  H, --COOH, and salts thereof; n is 2-3; m is 2-3; p is 1-10; and q is 1-18. 
     
     
       2. The agent of claim 1, where p is 1-4. 
     
     
       3. The agent of claim 1, where q is 1-6. 
     
     
       4. The agent of claim 1, where the paramagnetic metal is gadolinium. 
     
     
       5. The agent of claim 1, where R 1  is selected from the group consisting of: ##STR7## where R 2  is --C q  H 2q+1 , and q is 1--6. 
     
     
       6. An NMR contrast agent, comprising a complex of gadolinium with a ligand selected from the group consisting of compounds having the formula ##STR8## where R 1  is selected from the group consisting of: ##STR9## where R 2  is --C q  H 2q+1 , n is 2--3, m is 2--3, p is 1--4, and q is 1-6. 
     
     
       7. An NMR contrast-enhancing composition, comprising: a complex of a paramagnetic metal selected from the group consisting of gadolinium, manganese, iron, and chromium, with a ligand selected from the group consisting of compounds having the formula ##STR10## where R 1  is selected from the group consisting of: ##STR11## where R 2  is --C q  H 2q+1  ; X is selected from the group consisting of --SO 3  H, --COOH, and salts thereof; n is 2-3; m is 2-3; p is 1-10; and q is 1-18; and   a sterile solvent.   
     
     
       8. The composition of claim 7, where p is 1-4. 
     
     
       9. The composition of claim 7, where q is 1-6. 
     
     
       10. The composition of claim 7, where the paramagnetic metal is gadolinium. 
     
     
       11. The composition of claim 7, where R' is selected from the group consisting of: ##STR12## where R 2  is --C q  H 2q+1 , and q is 1-6. 
     
     
       12. An NMR contrast-enhancing composition, comprising: a complex of gadolinium with with a ligand selected from the group consisting of compounds having the formula ##STR13## where R 1  is selected from the group consisting of: ##STR14## where R 2  is --C q  H 2q+1 , n is 2-3, m is 2-3, p is 1-4 and q is 1-6; and   a sterile solvent.   
     
     
       13. A method of enhancing NMR contrast in a living subject, including administering internally to the subject an effective amount of a contrast agent which comprises a complex of a paramagnetic metal selected from the group consisting of gadolinium, manganese, iron, and chromium, with a ligand selected from the group consisting of compounds having the formula ##STR15## where R 1  is selected from the group consisting of: ##STR16## where R 2  is --C q  H 2q+1  ; X is selected from the group consisting of --SO 3  H, --COOH, and salts thereof; n is 2-3; m is 2-3; p is 1-10; and q is 1-18. 
     
     
       14. The method of claim 13, where p is 1-4. 
     
     
       15. The method of claim 13, where q is 1-6. 
     
     
       16. The method of claim 13, where the paramagnetic metal is gadolinium. 
     
     
       17. The method of claim 13, where R 1  is selected from the group consisting of: ##STR17## where R 2  is --C q  H 2q+1 , and where q is 1-6. 
     
     
       18. A method of enhancing NMR contrast in a living subject, including administering internally to the subject an effective amount of a contrast agent which comprises a complex of gadolinium with a ligand selected from the group consisting of compounds having the formula ##STR18## where R 1  is selected from the group consisting of: ##STR19## where R 2  is --C q  H 2q+1 , n is 2-3, m is 2-3, p is 1-4, and q is 1-6.